The purpose of this project is to develop an implantable chemotherapy system for sustained delivery of anti-cancer agents adjacent to the site of intraocular malignant tumors. The initial focus will be on laboratory studies of the effectiveness of nitrosourea compounds (particularly bischloroethyl nitrosourea, BCNU) against transplanted Greene melanoma in rabbit eyes. The drugs will be delivered adjacent to the tumor site through a silicone device implanted intra-or episclerally. Our objectives are: (1) to evaluate the capability of such drugs, when administered at a sustained rate, to destroy intraocular cancer cells, (2) to evaluate the efficacy of the BCNUimplanted silicone device system compared with conventional systemic administration, (3) to determine whether sustained delivery of the drug(s) through this system will achieve sustained concentration of the drug in the eye that is higher than achiveved by systemic administration and is also able to be tolerated by the animal. In vitro experiments: (1) study of the drugs' diffusion rates, with varying concentrations and solvents for the drugs, and through implant devices of varying materials; (2) study of stability of the drugs in various solvents; (3) study of effect of drug-containing implants on monolayers of cultured tumor cells; (4) microbiologic assay of drug concentration in ocular tissues and fluids, and of rate and duration of drug release from the implants. In vivo experiments: (1) determination of BCNU diffusion rate from silicone intrascleral and episcleral implants in normal rabbit eyes; (2) determination of cytocidal effect in the vitreous of intrascleral, episcleral, and subcutaneous implants by means of labelled tumor cell studies; (3) effectiveness of the chemotherapy system against experimentally produced melanoma in rabbit iris. Details of histological technique and method of detection of metastatic cells in the blood are presented.